1. Field of the Disclosed Subject Matter
The presently disclosed subject matter is related to coating interventional medical devices, and particularly coating of therapeutic agents on an expandable member of a medical device. More particularly, the presently disclosed subject matter relates to a system and method for retaining a therapeutic agent on a balloon during processing and delivery of the medical device.
2. Description of Related Subject Matter
Atherosclerosis is a disease affecting arterial blood vessels. It is a chronic inflammatory response in the walls of arteries, which is in large part due to the accumulation of lipid, macrophages, foam cells and the formation of plaque in the arterial wall. Atherosclerosis is commonly referred to as hardening of the arteries, although the pathophysiology of the disease manifests itself with several different types of lesions ranging from fibrotic to lipid laden to calcific. Angioplasty is a vascular interventional technique involving mechanically widening an obstructed blood vessel, typically caused by atherosclerosis.
During angioplasty, a catheter having a folded balloon is inserted into the vasculature of the patient and is passed to the narrowed location of the blood vessel, at which point the balloon is inflated to a fixed size as a result of fluid pressure inside the balloon. Percutaneous coronary intervention (PCI), commonly known as coronary angioplasty, is a therapeutic procedure to treat the stenotic coronary arteries of the heart, often found in coronary heart disease. In contrast, peripheral angioplasty, commonly known as percutaneous transluminal angioplasty (PTA), generally refers to mechanical widening of blood vessels other than the coronary arteries. PTA is most commonly used to treat narrowing of the leg arteries, especially, the iliac, external iliac, superficial femoral and popliteal arteries. PTA can also treat narrowing of veins, and other blood vessels.
Although the blood vessel is often successfully widened by angioplasty, sometimes the treated wall of the blood vessel undergoes vasospasm, or abrupt closure after balloon inflation or dilatation, causing the blood vessel to collapse after the balloon is deflated or shortly thereafter. One solution to this abrupt closure is stenting the blood vessel to prevent collapse. A stent is a device, typically a metal tube or scaffold, that is inserted into the blood vessel after, or concurrently with angioplasty, to hold the blood vessel open.
While the advent of stents eliminated many of the complications of abrupt vessel closure after angioplasty procedures, within about six months of stenting, a re-narrowing of the blood vessel can form. This is a condition known as restenosis. Restenosis was discovered to be a response to the injury of the angioplasty procedure and is characterized by a growth of smooth muscle cells—analogous to a scar forming over an injury. To address this condition, drug eluting stents were developed to reduce the reoccurrence of the narrowing of blood vessels after stent implantation. A drug eluting stent generally is a metal stent that has been coated with a drug that is known to interfere with the process of re-narrowing of the blood vessel (restenosis). Examples of various known drug eluting stents are disclosed in U.S. Pat. No. 5,649,977 to Campbell; U.S. Pat. No. 5,464,650 to Berg, et al.; U.S. Pat. No. 5,591,227 to Dinh, et al., U.S. Pat. No. 7,378,105 to Burke, et al., U.S. Pat. No. 7,445,792 to Toner, et al., and U.S. Pat. No. 7,335,227 to Jalisi, each of which is hereby incorporated by reference in its entirety. However, a drawback of drug eluting stents is a condition known as late stent thrombosis, which generally is an event wherein blood may clot on the stent.
Drug eluting balloons are believed to be a viable alternative to drug eluting stents in the treatment of atherosclerosis. In a study that evaluated restenosis, and the rate of major adverse cardiac events such as heart attack, bypass, repeat stenosis, or death in patients treated with drug eluting balloons and drug eluting stents, the patients treated with drug eluting balloons experienced only 3.7% restenosis and 4.8% MACE (major adverse cardiac events) as compared to patients treated with drug eluting stents, in which restenosis was 20.8% and 22.0% MACE rate. (See, PEPCAD II study, Rotenburg, Germany).
However, drug eluting balloons present certain unique challenges. For example, the drug carried by the balloon needs to remain on the balloon during delivery to the lesion site, and released from the balloon surface to the blood vessel wall when the balloon is expanded at the lesion site. For coronary procedures, the balloon is typically inflated for less than one minute, typically about thirty seconds. The balloon can be expanded for a longer period of time for peripheral procedures although this time rarely exceeds 5 minutes. Due to the short duration of contact of the drug coated balloon surface with the blood vessel wall, the balloon coating must exhibit efficient therapeutic agent transfer and/or efficient drug release during inflation. Thus, there are challenges specific to drug delivery via a drug coated or drug eluting balloon that are not presented by a drug eluting stent.
Conventional methods of loading interventional devices with therapeutic agents often require coating the entire surface of the balloon with the therapeutic agent. Coating of the entire surface can be performed in the inflated condition. For purpose of storage and shipping, as well as delivery through vasculature, the balloon is folded when deflated. However, once coated with a therapeutic agent, the balloon can become difficult to fold and sheath for assembly of the catheter. Further, conventional equipment and processes used to achieve such folding and assembly can cause damage, loss, or contamination of the therapeutic agent, and/or can result in contamination of the equipment. For example, conventional techniques for coating and folding the balloon require that the balloon be coated and subsequently dried in an expanded condition and thereafter collapsed into the completely folded configuration. This folding operation can cause fragmentation of the dried coating, which can dislodge from the balloon surface, and/or cracking, which effectively increases the surface area of the coating in contact with blood during delivery. Consequently, conventional coating and folding techniques can result in a drug loss of between 10% to 60% of the target dose.
Alternatively, balloons can be coated with a therapeutic agent while in a folded condition, thereby avoiding the drawbacks listed above. However, applying a coating of a solution to a folded balloon results in only a partially coated balloon surface area, which may not be desirable depending upon the needs and application. Furthermore, the entire surface area of a coating applied to the folded balloon is exposed to the blood stream during the tracking and delivery procedure, thus increasing the likelihood of losing a significant amount, if not all, of the drug coating before positioning the balloon and therapeutic agent at the desired location to commence treatment.
Thus, there remains a need for, and an aim of the disclosed subject matter is directed towards, a method with corresponding apparatus for assembly of an expandable member having one or more therapeutic agents coated thereon in such a manner that does not result in unacceptable damage or loss of therapeutic agent, nor significant contamination of the equipment employed, during processing or delivery of the medical device.